Device and method for cytology slide preparation

ABSTRACT

This invention provides a novel device and method for preparing cytology slides. The device comprises a book-like form including an absorbent material and filter attached to the inside surface of a front cover and a cytology slide removeably attached to an inside surface of a back cover. A sample is removed from the body of a patient, placed in a liquid-based solution, and then on the filter. When the book-like form is closed, the sample is effectively transferred to the slide. The device can be modified so that a plurality of slides are prepared at the same time.

FIELD OF INVENTION

[0001] The present invention relates generally to the preparation ofcytology slides and, more particularly, to a device and associatedmethod for preparing cytology slides.

BACKGROUND OF THE INVENTION

[0002] Cytology slides are prepared to screen and diagnose cellularsamples taken from, for example, samples from the uterine cervix, urine,sputum, blood, fine needle aspiration biopsy, urethral, bronchialbrushings and washings, cerebral spinal fluid, and other body fluids.The reliability and efficacy of the screening methods of these slidesare measured by their ability to diagnose infections, precancerouslesions or cancerous lesions while at the same time avoiding falsepositive or negative diagnosis. The reliability of these slides is aprimary issue. Often, the results are not accurate or are unreadable.Thus, there is a constant effort to improve the reliability and efficacyin the preparation of cytology samples.

[0003] One of the most common uses of cytology slides is for screeningand diagnosis of a cervical sample. Carcinoma of the cervix is one ofthe most common malignancies in women, causing nearly 5,000 deaths peryear in the United States. Approximately 60% of these cases areassociated with absent or deficient screening. Approximately 25% of thescreening failures are the result of errors in cervical sampling orsmear interpretation.¹

[0004] Screening for precancerous or cancerous changes of the uterinecervix traditionally involves microscopic assessment of cervicalPapanicolaou smears, called Pap smears. This traditional method forscreening requires scraping a woman's cervix with a sampling device,such as a cotton applicator stick, spatula or brush, and smearing thissample onto a slide for review by a medical lab professional. Thespecimen is gently spread across a slide to evenly distribute the cellsample. The slide is then fixed, stained, and examined under a lightmicroscope for cellular abnormalities.

[0005] In carrying out this operation, the portion of the cell samplethat is smeared onto the slide may contain blood, mucus, inflammatorycells, and clumps of cells. Accurate interpretation of up to 40% ofconventional Pap smears are compromised by the presence of blood,mucous, obscuring inflammatory cells, scant cellular material andair-drying artifacts.² The presence of these contaminants can obscuremany of the cells, causing important precancerous lesions to be missedwhen the slide is reviewed at the lab or, alternatively, making theentire slide unreadable.

[0006] One of the problems with the conventional Pap smear is howquickly the sample dries out once it is smeared on the slide. With aconventional Pap smear, the sample must be fixed immediately in order toavoid the drying out of the cells, which ruins the sample.

[0007] Another problem with the conventional Pap smear is the frequentinaccuracy of the test result. Common inaccuracies include both falsepositive and false negative Pap test results. A false positive Pap testoccurs when a patient is told she has abnormal cells when the cells areactually normal. A false positive result may require a woman to undergounnecessary and costly medical procedures. A false negative Pap testresult occurs when a specimen is called normal, but the woman has alesion. A false negative Pap test may delay the diagnosis and treatmentof a precancerous or even a cancerous condition.

[0008] The conventional Pap smear has false negative rates ranging from10-50%, with up to 90% of those false negatives due to limitations ofsampling or slide preparation.³ To decrease false negative ratesassociated with interpretation error, re-screening a portion of thenegative smear or recalling the patient for another sample is required.

[0009] Concern over the frequency of false-negative results of thetraditional Pap smear has led to the development of a variety of othertechnologies or clinical strategies, such as liquid-based cytologysystems, to improve Pap testing. For example, the Cytyc, Inc.(Marlborough, Mass.), ThinPrep® and the TriPath, Inc. (Burlington,N.C.), CytoRich® Pap test systems are two commercially available, FDAapproved fluid-based methods used for the collection and preparation ofcervicovaginal samples.

[0010] With the ThinPrep® system, a gynecologic sample is collected inthe same manner as the conventional Pap test using a broom-type deviceor plastic spatula and endocervical brush combination, but rather thansmearing the cytological sample directly onto a microscope slide, thismethod suspends the sample cells in a fixative solution (i.e.PreservCyt®). The ThinPrep® slide preparation system uses an automatedapparatus called a Cytyc 2000® that involves filtration using vacuumpressure and positive pressure-transfer steps to prepare cytologyslides.⁴

[0011] With the CytoRich® slide preparation system, the gynecologicsample is also collected in the same manner as the conventional Paptest. Like the ThinPrep® system, the CytoRich® system also places thesample in a liquid medium for further purification prior to analysis.CytoRich® specimens are processed using two centrifugation steps througha gradient solution to separate the diagnostic cells from theinterferring material. The cells are ultimately re-suspended in a finalpreparation that is applied to the slide using a special pipettingapparatus (Autocyte Prep System®) provided by the manufacturers(Tripath, Inc.). This transfer step can also be performed manually.Thereafter, a sample is placed on a slide and analyzed by cytology.

[0012] These new methods have demonstrated increased quality in thepreparation of the sample, improved detection rates, and a reduced needfor patients who must return for repeat smears. However, in both theThinPrep® and the CytoRich® slide preparation systems, a time consumingand expensive procedure is followed to prepare a mono-dispersed layer ofcells on a cytology slide.

[0013] Although each of these systems reduces significantly thefalse-negative rate of the traditional Pap smears, the health caremarket has been slow in adopting these systems because of their cost andpreparation time compared to the conventional Pap smears.

SUMMARY OF THE INVENTION

[0014] The invention provides a device and a method of using the devicethat overcomes these problems. The device and associated method providea better quality prepared cytology slide having a more even distributionof cells with less interference from debris than the conventional Papmethod, while offering an easier, quicker and more economical procedureas compared to known liquid-based medium methods. Thus the device andassociated method facilitate the preparation and screening process ofcytology slides.

[0015] According to one embodiment, a device for facilitating thepreparation of cytology slides comprises a first cover having an insidesurface, a second cover having an inside surface and an interposedspine. The spine may be replaced by one or more hinges. The first andsecond cover are pivotably secured to the spine so as to be foldableinto a book form capable of an open and closed position. An absorbentmaterial is mounted on the inside surface of the first cover and afilter overlays the absorbent material. The cytology slide is removeablymounted to the inside surface of the second cover. The slide ispositioned on the inside surface of the second cover to contact with thefilter when the book-like device is in the closed position.

[0016] In another aspect, the invention is directed to a method ofpreparing cytology slides. The method comprises combining a cellularsample with a liquid-based medium to create a solution, mixing thesolution, extracting the sample or an aliquot of the sample from thesolution and providing a slide preparation device. The device comprisesa first cover having an inside surface, a second cover having an insidesurface and an interposed spine. The first and second cover arepivotably secured to the spine so as to be foldable into a book form. Anabsorbent material is mounted to the inside surface of the first coverand a filter overlays the absorbent material. A slide is removeablymounted to the inside of the second cover so that the filter contactsthe slide when the device is in the closed position. The method furthercomprises applying the sample to the filter, closing the book form sothat the filter containing the sample contacts the slide, and applying apressure to the contact surface to effectively transfer the specimen tothe slide. The range of pressures appropriate for the absorbent matterand the filter in the device is provided by the design of the device. Inthis way, a cytology slide containing an evenly distributed number ofcells is prepared quickly and reliably.

[0017] In another aspect of the invention, the invention is directed toa device for facilitating the preparation of a plurality of cytologyslides at the same time. The device comprises a cover having an insidesurface, a base having an inside surface, and an interposed hinge. Thecover and base pivotably secure to the hinge so as to be foldable into abook form capable of an open and closed position. A plurality ofabsorbent material are mounted on the inside surface of the cover and afilter overlays the absorbent material. A plurality of cytology slidescorresponding to one of the absorbent material are mounted to the insidesurface of the base. Each slide is positioned on the inside surface ofthe base to contact the corresponding absorbent material and the filterwhen the book form is in the closed position

BRIEF DESCRIPTION OF THE DRAWINGS

[0018]FIG. 1A is an exploded view of one embodiment of the devices;

[0019]FIG. 1B is an isometric view of one embodiment of the device;

[0020]FIG. 1C is an isometric view of one embodiment of the device;

[0021]FIG. 2A is an isometric view of another embodiment of the deviceillustrating a single continuous hinge;

[0022]FIG. 2B is an isometric view of one embodiment of the deviceillustrating a hinge having a number of interlocking pieces 34;

[0023]FIG. 3 is an isometric view of another embodiment of the deviceillustrating a pocket 46 and fastening means 60;

[0024]FIG. 4A is a partial view of the front cover of one embodiment ofthe device illustrating the recess or well 36;

[0025]FIG. 4B is a partial view of the front cover of one embodiment ofthe device illustrating the absorbent material and filter extendingabove the inner surface; and

[0026]FIG. 5 is a partial view of the front cover of one embodiment ofthe device illustrating a plurality of supports

[0027]FIG. 6A illustrates the cell distribution of a cervical sampleusing the device and method of the present invention.

[0028]FIG. 6B illustrates the cell distribution of a conventional Papsmear (archival)at a magnification of ×120.

[0029]FIG. 7 illustrates an exploded view of an embodiment of the devicecapable of preparing multiple cytology slides at the same time.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0030] Hereinafter, the invention will be described in greater detailwith reference to the preferred embodiments. However, it is understoodthat the device and associated method of the invention are applicablefor the preparation of cytology slides for any cellular or tissuesamples, preferably clinical cellular samples, known in the art.

[0031] Referring now to FIG. 1A, in one embodiment of the invention, akit 100 for facilitating the preparation of cellular samples includes adevice 10 comprising a front cover 12, a rear cover 16, and a spine 24connecting the front and rear covers 12, 16. The spine 24 spaces thefront cover 12 and the back cover 16 when folded in the closed positionand creates a book-like form, wherein the inside 14 of the front cover12 and the inside 18 of the back cover 16 face and contact against eachother. In an alternative embodiment illustrated in FIG. 1A, the frontcover 12 does not need to be the same size as the back cover 16.

[0032] The covers 12, 16 and spine 24 may be made of a single piece offlexible material. Such flexible material can include, for example,cardboard or some flexible plastics to which a controlled pressure maybe applied to the outside covers 12, 16 without puncturing or crackingthe covers. The material should not absorb the sample or solutionapplied to the filter 22 and absorbent material 20 (described in moredetail below). The material should also be selected to enable varioususers, such as, for example, lab technicians and doctors, to applyconsistent or controlled amount of pressure to prevent over squeezingthe solution, resulting in spillage or distortion of the morphology ofthe sample by the exertion of too much pressure.

[0033] Alternatively, the device 10 can be made from an inflexiblematerial. Such inflexible material can include, for example, wood,wood-derived materials, metals or inflexible plastics. When inflexiblematerials are used for the front and back covers, it may be preferableto use one or more hinges to connect the front and back covers. In theembodiment illustrated in FIGS. 2A and 2B, a hinge 30 connects the frontcover 12 and back cover 16. The hinge 30 is constructed so that thefront cover 12 and back cover 16 face and contact each other when thebook form is in the closed position. The hinge 30 can be one single,continuous piece 32 (FIG. 2A) or, alternatively, a number of flexible orinterlocking pieces 34 (FIG. 2B).

[0034] In FIG. 1B, the device is shown in the open position. Front cover12 is flipped open, exposing an absorbent material 20 and a filter 22attached to the inside 14 of the first cover 12. A slide 40 is alsoshown mounted to the inside 18 of the back cover 16 of the device 10.

[0035] The absorbent material 20 is hydrophilic in nature. Inparticular, the absorbent material is absorbent to both water andalcohol-based solutions and is preferably uniform in its absorbency. Theabsorbent material is preferably inert and stable so as not to reactwith the alcohol solution or components of the cellular sample. Theabsorbent material preferably possesses stability properties enablingthe finished device to be stored for several years. Standard filterpapers or blotting papers may be used as an absorbent material. Forexample, one suitable absorbent material is that sold by Bio-Rad®(Hercules, Calif.) called Absorbent Filter Paper (Extra Thick)consisting of 100% cotton fiber. Alternatively, the absorbent materialcan be 100% double-sided, twill-pattern woven cotton (e.g. WipersNatural; TX306 made by TexWipe® Company), or polyvinyl acetal foam(HydroSpong™; TX5390 made by Tex Wipe® Company), Gelman's® AbsorbentPad, Cellulose Fiber Filter Pad, Whatman's® Glass Microfibre filters,Whatman's® cellulose paper, TexWipe® Company (Upper Saddle River, N.J.)trademarked Absorbond® (Wipers Synthetic; TX404) consisting of 100%hydro-entangled polyester, Denville® Scientific Hyblot Mater, Millipore®cellulose absorbent pads or any other absorbent material or combinationof materials known in the art.

[0036] The absorbent material 20 adheres to the inside 14 of the frontcover 12 by, for example, an adhesive or, alternatively, by a heat spotweld. It should be understood that the adhesive is selected so as not tointerfere with the properties of the absorbent material, as mentionedabove. One such suitable adhesive is gel cyanoacrylate sold by Loctiteunder the trademark Loctite 4541®. Alternatively, the adhesive can behot melt or acrylic or synthetic rubber based adhesives or any adhesiveknown in the art.

[0037] The filter 22 overlays the absorbent material 20. Any filterknown in the art can be used. The filter 22 is preferably apolycarbonate film containing approximately 3 to 8 micrometer pores. Thepore sizes can be varied to enable the filter to capture the desiredcells on the surface of the filter while allowing the debris to passthrough to the absorbent material 20. The filter should also be inert,stable, and alcohol resistant. Alternatively, the filter can be nylon,cellulose, polyester, teflon, polytetrafluorethylene or any other filtermaterial known in the art.

[0038] An adhesive to attach the filter 22 to the absorbent material 20is selected so as not to interfere with the sample placed on the filter20. Revertex Chemicals Ltd. (Malaysia) sells some suitable adhesives forattaching the filter 22 to the absorbent material 20, such as, forexample, starch, dextrin, latex and casein. Alternatively, the adhesivecan be ethylene vinyl acetate and polyvinyl acetate emulsion adhesivefor lamination of the filter 22 and the absorbent material 20. In otherembodiments, the filter 22 can be held in proximity to the absorbentmaterial 20 by mechanical means, such as, for example, a rim of plasticto hold the overlapping filter 22 onto the absorbent material 20 disk.

[0039] The slide 40 is a standard slide, made of either glass orplastic, commonly used in cytology. In the embodiment of FIG. 1A, theslide 40 is mounted to the inside 18 of the back cover 16 in such a waythat enables the slide 40 to be easily removed. In the embodiment ofFIG. 1B, the slide 40 is mounted to the inside 18 of the back cover 18by a piece of adhesive or tape 42. However, any commonly known methodknown in the art that accomplishes this goal can be used to mount theslide. For example, the slide 40 can be press-fit into a cutout portion44 of the inside 18 of the back cover 16, held by Velcro® strap, orplaced in a pocket 46 formed in the inside 18 of the back cover 16 (FIG.3) to facilitate removal of the slide 40.

[0040] In another embodiment, the inside 18 of the back cover 16includes finger recesses 28 to aid a user in lifting the slide 40 out ofthe back cover (FIGS. 1B and 1C). The finger recesses 28 should bepositioned away from the preparation area to avoid contamination of thetransferred sample.

[0041] The absorbent material 20 with the attached filter 22 arepositioned on the inside 14 of the front cover 12 of the book-likedevice 10 so that when the book-like device 10 is closed, the filter 22contacts a central location on the slide 40.

[0042] In another embodiment, as illustrated in FIG. 4A and 4B, theabsorbent material is placed in a recess or shallow well 36 formed inthe inside 14 of the front cover 12 so that the upper portion of theabsorbent material 20 having the overlaying filter 22 (as will bedescribed in more detail below) extends above the inside surface 14 ofthe front cover 12. This recess or shallow well 36 provides the addedbenefit of holding any excess solution that escapes from the bottom ofthe absorbent material 20. In yet another embodiment, the absorbentmaterial 20 is held in place on the inside 14 of the front cover 12 by aplurality of supports 50, as illustrated in FIG. 5.

[0043] When the book-form is closed, the inside 14 of the front cover 12and the inside 16 of the back cover 10 contact each other. In theembodiment in which the upper portion of the absorbent material 20 andfilter 22 extend above the inside surface 14 of the front cover 12,there is no need to exert an additional pressure to transfer the sampleto the slide 40 from the filter 22, when the back cover 10 comes intocontact with front cover 12. The slide 40, which can be flush with theinside 18 of the back cover 16 will compress the absorbent material 20and filter 22, thus transferring the sample to the slide 40.

[0044] As illustrated in FIG. 3, the kit 100 may optionally include amechanical fastening means 60 to lock together and maintain the contactof the inside surfaces 14, 18 of the front and back covers 12, 16,respectively, when the book-form device 10 is closed. Any mechanicalfastening means known in the art, such as Velcro®, tape, clasps, snaps,or the like, can be used. When the book-form device 10 is closed,causing the filter 22 to contact the slide 40, the appropriate amount ofcontrolled pressure may be applied by fastening the fastening means 60.In an embodiment including a clasp or snap fastening means 60, anaudible snap is preferably heard when the fastening means is fastened.This audible snap informs the user that a controlled amount of pressureis being applied to transfer the sample from the filter 22 to the slide40.

[0045] A cellular sample is any cellular or tissue specimen collectedfrom a subject for the purposes of screening or diagnosing, commonlyknown in the art, that is capable of being suspended in a liquid-basedmedium. Such samples are obtained, for example, from the cervix, themouth or throat, urine sediments, lymph nodes, esophagus, bronchial,breast (i.e. nipple discharge), skin lesions, thyroid, blood anddisruptive tissue biopsies.

[0046] In the present invention, the kit 100 is used to prepare acytology slide with a mono-dispersed cell sample. In the broader aspectsof the invention, there is no limitation on the collection and handlingof samples as long as consistency is maintained. The cell or tissuesample is obtained by methods known in the art, such as, biopsies,surgical resections, standard bodily fluid collection techniques or thelike.

[0047] In an embodiment in which the cellular sample is a cervicalsmear, the sample is taken from the cervix. The present inventionemploys standard techniques for collecting cervical cells; for example,it generally involves the insertion of a cervical brush or broom deviceand the taking of cells from the surface of the cervix and theendocervix.

[0048] The cellular sample is preferably placed in any liquid-basedcytology medium used and known in the art. One example of such acytology medium is known as a Universal Collection Medium (UCM) fromDigene Corp. (Gaithersburg, Md.). UCM is a cell collection medium whichpreserves both cell morphology and cellular biomolecules forquantitative analysis in a cell sample so that multiple assays can becarried out from a single patient sample .⁵ Other liquid-based cytologymedia can be used, such as PreservCyt® from Cytyc, Inc. (Boxborough,Mass.) and CytoRich® Preservative Fluid from TriPath, Inc. (Burlington,N.C.).

[0049] One preferred method places the cellular sample in 1 milliliterof UCM. This solution is then suspended, by mixing. Mixing can beconveniently achieved, for example by vortexing the solution forapproximately five to ten seconds.

[0050] After suspending the cells, a sample is removed carefully,usually with a pipette, and placed on the filter 22. If one milliliterof UCM is used, it may be preferable to use an aliquot of approximately200 microliters from the solution. This sample is then applied to thesurface of the filter 22. One skilled in the art understands that otherliquid media may be used and the sample may be suspended in varyingamounts of such media. The solution and other debris pass through thefilter 22 to the absorbent material 20 while the cells are captured onthe surface of the filter 22. The book-like device 10 is then closed sothat the filter 22 contacts the slide 40 for about 15 seconds while amoderate pressure, created when the covers are closed and lockedtogether, is applied to the front and back covers 12, 16, respectively.The device or user applies from 200 to 1000 grams of pressure to theslide and specimen for optimum transfer of the cytology specimen to theslide.

[0051] The pressure applied to the covers 12, 16 transfers the cellscaptured by the filter 22 to the slide 40. After the pressure isapplied, the slide 40 can be removed from the book-like device 12 andfixed and stained in the routine manner.

[0052] In order to optimally preserve the cell detail and maintain themorphologic characteristics, without distortion, the cells arepreferably wet-fixed before any air drying occurs.

[0053] Conventional methods known in the art can be used for fixing,staining and analyzing the sample. The following provides a generaloutline of such conventional techniques but should not be construed tolimit the applicability of the invention to the alternative cytologypreparation techniques known in the art.

[0054] Most laboratories use a 95 percent ethanol solution for mostroutine preparations that require fixations. However, other fixativesknown in the art can be used. Most of these fixatives are composed ofpolyethylene glycol in an alcohol base and are applied either from adropper bottle or in spray form. Coating fixatives are also widely usedfor cervical smears. These fixatives cover the sample in a waxy coatingthat protects it from damage.

[0055] One advantage of using the absorbent material 22 is that the cellsample will not dry out as quickly. When the book-like device 10 isclosed, the absorbent material 22 keeps the sample moist as it istransferred to the slide since a liquid-based solution is used and theabsorbent material 20 is held in close physical proximity to thespecimen. The device 10 maintains a “moist” or “humid” environment sothat the cells can be preserved in the device 10 before fixing for up to30 minutes following application on the slide 40. Once on the slide 40,the cell sample should be preserved as mentioned above.

[0056] After the cells are transferred to the slide and the cells arefixed, the cellular sample is generally stained. Staining may berequired to retain the transparency of the cells and display variationsof cellular maturity and metabolic activity. Any stain or stainingmethod known in the art can be used.⁶ The universal stain forcytological preparations is the Papanicolaou stain. Alternatively, anystain known in the art, such as Hematonylin and Eosin stain or specialchemical stains or immunochemical stains, or in-situ hybridization canbe used.

[0057] Once any staining technique has been completed, the slide may bemounted in a suitable medium satisfactory for microscopy. There are manycommercially available mountants that can be used that are well known inthe art. These mountants protect the sample from dust and damage andshould harden rapidly and not discolor or crystallize during long-termstorage.

[0058] A coverslip may then be placed over the sample. Coverslipping hastraditionally been achieved using a thin glass slip (less than 0.17millimeters) or continuous film. Various sizes are commerciallyavailable but the entire sample preparation should be covered by themountant and the coverslip.

[0059] Referring now to FIG. 7, in another embodiment of the invention,a kit 200 for facilitating the preparation of a plurality of cellularsamples includes a cover 210, a base 230 and at least one hinge 205 forclosing cover 210 over base 230 to create a book-like form.

[0060] The cover 210 and base 230 may be made of a single piece offlexible material. Such flexible material can include, for example,cardboard or some flexible plastics to which a controlled pressure maybe applied to the outside surface of the cover without puncturing orcracking the cover. The material should not absorb the sample orsolution applied to the filters and absorbent material, as described inmore detail above. The material should also be selected to enablevarious users, such as, for example, lab technicians and doctors, toapply consistent or controlled pressure to prevent over squeezing thesolution, resulting in spillage or distortion of the morphology of thesample by the exertion of too much pressure.

[0061] Alternatively, cover 210 and base 230 can be made from aninflexible material. Such inflexible material can include, for example,wood, wood-derived materials, metals or inflexible plastics. In oneembodiment, the weight of the material used for the cover providesenough pressure to effectively transfer the sample from the absorbentmaterial and filter onto the cytology slide. In experimenting with theappropriate weight to be applied to effectively transfer the sample,over one hundred slides were prepared using the method discussed aboveand weights up to 1200 grams were applied to the cover 210. The slideswere then fixed, stained and evaluated. Based on the morphologicalevaluation, it was determined that the cell morphology was altered, e.g.the nuclei were slightly enlarged, when weights close to 1200 grams wereused. It was also determined that the used of weights of less than 300grams did not effectively transfer the samples from the absorbentmaterial and filter to the slides.

[0062] In an alternative embodiment, clamps can be used to close cover210 and base 230 so that the samples may be effectively transferred.

[0063] The cover 210 supports a strip 212 holding a plurality of piecesof absorbent material 20 and a filter strip 22 overlaying the absorbentmaterial 20. The absorbent material 20 and filter 22 are made from thesame materials discussed above. In alternate embodiments, separatefilters corresponding to each piece of absorbent material 20 held by thestrip 212 or, alternatively, a filter 22 overlaying a number of piecesof absorbent material 20 can be used.

[0064] The upper portion of the absorbent material 20 and filter 22extend above the top surface of strip 212 so that when cover 210 isclosed over base 230, the samples applied to the absorbent material 20and filter 22 are effectively transferred to the corresponding slides 40held by slide carrier 232.

[0065] The strip 212 holding absorbent material 20 and filter 22 issupported by cover 210 in a channel 214 formed in the inside surface 216of the cover 210. In one embodiment, strip 212 is press fit into thechannel 214. In another embodiment, strip 212 includes feet 220projecting from the bottom side of strip 212 which are press fit intorecesses 222 formed in the bottom surface 213 of channel 214. The feet220 also serve to stabilize and position strip 212 in relation to cover210 and keep the strip 212 from sliding out of the channel 210. Inanother embodiment, strip 212 can be slid into and resiliently held bychannel 214.

[0066] The strip 212 can also include positioning members 226 projectingfrom the sides of strip 212. Positioning members 226 are received byrecesses 227 formed in the sides of channel 214 to ensure that strip 212is properly positioned in channel 214.

[0067] The absorbent material 20 is adhered to the top surface of strip212 by, for example, an adhesive or, alternatively, by a heat spot weld.It should be understood that the adhesive is selected so as not tointerfere with the properties of the absorbent material, as mentionedabove. Alternatively, the adhesive can be hot melt or acrylic orsynthetic rubber based adhesives or any adhesive known in the art. Thefilter overlays the adhesive pad in the same manner as discussed above.

[0068] The base 230 supports a slide carrier 232 capable of holding aplurality of slides 40. The number of slides 40 held by slide carrier232 corresponds to the number of pieces of absorbent material 20 onstrip 212 supported by cover 210.

[0069] The slide carrier 232 containing slides 40 is supported by base230 in a channel 234 formed in the top surface of base 230. In oneembodiment, slide carrier 232 is press fit into channel 234. In anotherembodiment, slide carrier 232 includes feet (not shown) projecting fromthe bottom side of slide carrier 232. The feet are press fit intorecesses 238 formed in the bottom surface of channel 234. The slidecarrier 232 can also include positioning members, similar to positioningmembers 236 on strip 212, projecting from the sides of slide carrier 232to ensure that slide carrier 232 is properly positioned in channel 234.

[0070] The slide carrier 232 includes a plurality of slots 240 separatedby ridges or dividers 242 for securely holding slides 40 in place whenthe kit 200 is opened and closed. While slide carrier 232 is held inchannel 234 in base 230, the top surface 244 of dividers 242 is flushwith the top surface of base 230 to ensure proper closing of kit 200.Finger recesses 250 may be provided to facilitate the insertion andremoval of the slides 40 from slide carrier 232.

[0071] In an alternate embodiment, the slide carrier 232 can behingeably attached to base 230. In another embodiment, the slides 40 areinserted into separate, individual slots formed in the base 230 itself.

[0072] The method of applying or smearing a sample to any of theabsorbent materials 20 and filter 22 and transferring the sample to theslide 40 is identical to the method described above for the book-likedevice 10. With the kit 200, one lab technician or doctor can preparemultiple slides at the same time.

[0073] Once the samples are transferred and the slides are prepared, theslides may be individually analyzed or stored in slide carrier 232 forfuture analysis.

EXAMPLE

[0074] Comparison with Conventional Pap Smear

[0075] A cervical sample was taken from a female patient and placed in aone milliliter of Universal Collection Medium.⁷ An aliquot of 200microliters is removed from the solution and applied to the surface ofthe filter 22 of the book-form device 10. The book-form device 10 wasclosed for approximately 15 seconds while a controlled amount ofpressure was applied. The slide 40 was then removed from the book-formdevice 10 and the sample was fixed, stained and placed under a lightmicroscope. FIG. 6A shows the morphology of cervical cells prepared bythe method of the present invention.

[0076]FIG. 6B was taken from archived routine Pap smears to show themorphology, distribution of cells and staining of stored samples fixedto slides for comparison. The morphology of the cells prepared by themethod of the present invention shows better quality and more evenlydistributed cells with less interference from debris than theconventional Pap smear.

[0077] Table 1, below, shows a comparison of Pap slides from the samepatients made with the conventional Pap smear technique and the UCMbook-form device Pap slide technique. These results demonstrate completeagreement between the two procedures. TABLE 1 UCM vs. Conventional Pap*Case ID Conventional Pap UCM Manual Pap  1W WNL WNL  2W LSIL HSIL  3WWNL WNL  4W WNL WNL  5W WNL WNL  6W WNL WNL  7W WNL WNL  8W WNL WNL  9WWNL WNL 10W WNL WNL 11W WNL WNL 12W WNL WNL 13W WNL WNL 14W WNL WNL 15WWNL WNL

[0078] It will be apparent to those skilled in the art that variousmodifications and variations can be made in the device and method of thepresent invention without departing from the spirit or scope of theinvention. Thus, it is intended that the present invention embraces allsuch modifications and variations within the spirit and scope of theappended claims.

[0079] All articles, patents or other references cited or referred toherein are hereby incorporated herein in toto by reference.

REFERENCES

[0080]¹Sawaya, George F. (M.D.), Grimes, David A. (M.D.), “NewTechnologies in Cervical Cytology Screening: A Word Of Caution”,Obstetrics and Gynecology, 1999, Vol. 94, pg.1, which is incorporatedherein by reference.

[0081]²Davey D D, Nielsen M L, Rosenstock W, Tilde TS. “Terminology andspecimen adequacy in cervicovaginal cytology: The College of AmericanPathologists interlaboratory comparison program experience”, Arch. Path.Lab. Med. 1992, vol. 116, pgs. 903-907 which is incorporated herein byreference.

[0082]³van der Graaf Y, Vooijs G P, Gaillard H L J, Go DMDS, “Screeningerrors in cervical cytological screenings”, Acta Cytologica, 1987, vol.31, pgs. 434-8; Dehner L P, “Cervicovaginal cytology, false-negativeresults, and standards of practice”, Am. J. Clin. Pathol, 1993, vol. 99,pgs. 45-47; Gay J D, Donaldson L D, Goetliner J R., “False negativeresults in cervical cytologic studies”, Acta Cytologica, 1985, vol. 29,pgs. 1043-1046; and Morell, N D, Taylor J R, Snyder R N, Ziel H K, SaltzA, Willis S., “False-negative cytology rates in patients in whominvasive cerviocal cancer subsequently developed”, Obstet. Gynecol.,1982, vol. 60, pgs. 41-45 which are incorporated herein by reference.

[0083]⁴ Further information about the operation and efficiency of theThinPrep® method is set forth in Obstetrics & Gynecology, Vol. 90, No.2, pps. 278-284 in an article by Lee, Ashfaq, Birdsong, Corkill,McIntosh and Inhorn titled “Comparison of Conventional PapanicolaouSmears and a Fluid-Based, Thin-Layer System for Cervical CancerScreening” which is incorporated herein by reference.

[0084]⁵Further information about the UCM is set forth in PCTInternational Application No. PCT/US98/26342 (European patentapplication number 98962066.1), filed on Dec. 11, 1998 by Attila T.Lorincz and Yanlin Tang for a Universal Collection Medium which isincorporated herein by reference.

[0085]⁶Further information about fixation and staining methods andmaterials used is provided by the Health Care Financing Administrationand set forth in “The Tutorial of Cytology” by Wied, Keebler, Koss andReagan (1998, pps. 580-583), and in “Comprehensive Cytopathology” byBibbo, (1991, pps. 882-892) which are incorporated herein by reference.

[0086]⁷Further information about the UCM is set forth in PCTInternational Application No. PCT/US98/26342 (European patentapplication number 98962066.1), filed on Dec. 11, 1998 by Attila T.Lorincz and Yanlin Tang for a Universal Collection Medium which isincorporated herein by reference.

We claim:
 1. A device for facilitating the preparation of cytologyslides, the device comprising a first cover having an inside surface; asecond cover having an inside surface; an interposed spine, said firstand second cover pivotably secured to the spine so as to be foldableinto a book form capable of an open and closed position; an absorbentmaterial mounted on the inside surface of the first cover; a filter, thefilter overlays the absorbent material; and a cytology slide, whereinthe cytology slide is removeably mounted to the inside surface of thesecond cover, the slide being positioned on the inside surface of thesecond cover to contact the filter when the book form is in the closedposition.
 2. The device of claim 1, wherein the filter is polycarbonate.3. The device of claim 1, wherein the absorbent filter is a polyvinylacetal foam.
 4. The device of claim 1, wherein the absorbent filter is100% cotton fiber.
 5. A device for facilitating the preparation ofcytology slides, the device comprising: a first cover having an insidesurface; a second cover having an inside surface, the second coverhingeably attached to the first cover so as to be foldable into a bookform capable of an open and closed position; an absorbent materialmounted on the inside surface of the first cover; a filter, the filteroverlays the absorbent material; and a cytology slide, wherein thecytology slide is removeably mounted to the inside surface of the secondcover, the slide being positioned on the inside surface of the secondcover to contact with the filter when the book form is in the closedposition.
 6. The device of claim 5, wherein the hinge is a single,continuous piece.
 7. The device of claim 5, wherein the hinge is aplurality of interconnected pieces.
 9. A method of preparing cytologyslides, the method comprising: combining a cellular sample with aliquid-based medium to create a solution; removing an aliquot from thesolution; providing a slide preparation device comprising a first coverhaving an inside surface, a second cover having an inside surface, saidfirst and second cover pivotably secured to each other so as to befoldable into a book form, an absorbent material mounted to the insidesurface of the first cover, a filter, the filter overlays the absorbentmaterial and a slide attached to the inside surface of the second cover;applying the aliquot to the filter; closing the book form so that thefilter containing the aliquot contacts the slide; and applying apressure to the first and second covers.
 10. The method of claim 9,wherein the liquid-based medium is a Universal Collection Medium.
 11. Adevice for facilitating the preparation of a plurality of cytologyslides, the device comprising a cover having an inside surface; a basehaving an inside surface; an interposed hinge, said cover and basepivotably secured to the hinge so as to be foldable into a book formcapable of an open and closed position; a plurality of absorbentmaterial mounted on the inside surface of the cover; a filter, thefilter overlaying the absorbent material; and a plurality of cytologyslides, each cytology slide corresponding to one of the absorbentmaterial mounted on the cover, wherein the cytology slides are mountedto the inside surface of the base, each slide being positioned on theinside surface of the base to contact the corresponding absorbentmaterial and the filter when the book form is in the closed position.12. The device of claim 11, wherein the slides are removeably mounted onthe inside surface of the base.
 13. The device of claim 12, wherein theslides are removeably mounted to a slide carrier, the slide carrier isremoveably mounted to the inside surface of the base.
 14. The device ofclaim 12, wherein the slides are removeably mounted to a slide carrier,the slide carrier is hingeably mounted to the inside surface of thebase.
 15. The device of claim 11, wherein the absorbent material ismounted to a strip, the strip is removeably mounted to the insidesurface of the cover.
 16. The device of claim 11, wherein the filterincludes a plurality of individual filters, each filter corresponding toone of the absorbent materials.
 17. The device of claim 11, wherein thecover is weighted to effectively transfer a sample applied to theabsorbent material and filter to the slide when the book form is in theclosed position.
 18. A slide carrier suitable for use with the device ofclaim 11, said slide carrier including a plurality of slots for holdinga plurality of cytology slides, wherein the slide carrier is removeablymounted to the base of the device.
 19. A strip suitable for use with thedevice of claim 11, said strip holding the plurality of absorbentmaterial, wherein the strip is removeably mounted to the cover of thedevice.